Antibiotics in Feed Induce Prophages in Swine Fecal Microbiomes

Antibiotics are a cost-effective tool for improving feed efficiency and preventing disease in agricultural animals, but the full scope of their collateral effects is not understood. Antibiotics have been shown to mediate gene transfer by inducing prophages in certain bacterial strains; therefore, one collateral effect could be prophage induction in the gut microbiome at large. Here we used metagenomics to evaluate the effect of two antibiotics in feed (carbadox and ASP250 [chlortetracycline, sulfamethazine, and penicillin]) on swine intestinal phage metagenomes (viromes). We also monitored the bacterial communities using 16S rRNA gene sequencing. ASP250, but not carbadox, caused significant population shifts in both the phage and bacterial communities. Antibiotic resistance genes, such as multidrug resistance efflux pumps, were identified in the viromes, but in-feed antibiotics caused no significant changes in their abundance. The abundance of phage integrase-encoding genes was significantly increased in the viromes of medicated swine over that in the viromes of nonmedicated swine, demonstrating the induction of prophages with antibiotic treatment. Phage-bacterium population dynamics were also examined. We observed a decrease in the relative abundance of Streptococcus bacteria (prey) when Streptococcus phages (predators) were abundant, supporting the “kill-the-winner” ecological model of population dynamics in the swine fecal microbiome. The data show that gut ecosystem dynamics are influenced by phages and that prophage induction is a collateral effect of in-feed antibiotics.